Golgi staining reveals the anatomical structure of dendrites. While Golgi methods have yielded some of the most robust histological findings in schizophrenia, studies that use these techniques are uncommon, probably because the techniques have been difficult to apply and notoriously capricious. We have developed a new modification of the Golgi-Cox method that has yielded unprecedented reliability, with consistent staining in over 100 consecutive blocks from over 70 consecutive autopsy cases. There is a uniform distribution of stained neurons that allows systematic random sampling of neurons for analysis. We propose to use this material to study dendritic arborization and spine density in 20 schizophrenia subjects matched by age and sex to 40 subjects without psychiatric disease, all evaluated clinically by psychological autopsy. We will analyze dendritic arborization and spine density in dorsal (BA9) and ventral (BA45) prefrontal cortex, and in the hippocampal formation (subiculum, CA3, CA1, and dentate gyrus). Since every section cut from a block is stained well, we propose to share the slides with other laboratories that wish to perform additional analyses. This application also includes continuation of our ongoing collection of brain specimens and psychological autopsies in the Republic of Macedonia. This collection provides the fresh tissue for our Golgi studies and for many other studies of the neurobiology of psychiatric illnesses, both in our department and at other institutions. The specimens and data are stored in our department and subjected to rigorous clinical, neuropathological, and toxicological review. PUBLIC HEALTH RELEVANCE: Schizophrenia is a devastating illness that affects 1% of the population. The structural abnormalities of the brain that underlie schizophrenia are poorly understood, but they are likely to involve the dendritic processes that extend outwards from neurons. We have developed improved procedures to visualize these processes in human brain tissue from autopsies, and we will use these methods to determine whether there are consistent abnormalities of brain structure in schizophrenia.